Ovarian cancer is one of the deadliest of all major cancers. While early stage disease is generally curable with surgery, most women are diagnosed because of symptoms which are a harbinger of advanced disease. This underscores the urgency for screening asymptomatic women. However, none of the current techniques are clinically recommended because of the inability to accurately identify at-risk women. Therefore, it is mandatory to develop a highly accurate, minimally intrusive, inexpensive test that targets clinically important (aggressive) disease at an early stage. Ideally this could be coupled with the Pap smear program. We propose a new ovarian cancer screening strategy based on identifying ovarian field cancerization at a clinically practical site (endometrium or cervix) through our novel biophotonics approach analogous with our successful programs in the colon, lung and pancreas. The feasibility of the approach is underscored by the fact that the most aggressive serous subtype of ovarian cancer (by far the leading cause of ovarian cancer mortality) initially develops outside of the ovary, in the fimbrae of the fallopian tubes. Accordingly, other areas of the gynecological tract that are contiguous with the fallopian tubes (e.g. endometrium and endocervix) have been shown to exhibit field carcinogenesis alterations. Although microscopically normal, cells in this field acquire a number of alterations including genetic, epigenetic and nanoarchitectural. This presents an opportunity to risk- stratify for ovarian cancer through detection of the field effect in a readily accessible site such as endometrium or cervix. More rigorous and aggressive evaluation of these patients would then be warranted. These nanoarchitectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy. Our pilot data show that the alteration of nanoscale architecture in endometrial and cervical cells is exquisitely sensitive to field carcinogenesis and, hence, may serve as a robust biomarker for ovarian cancer. In this study, we will explore the feasibility of using PWS to detect these nanoscale alterations focusing on early stage, curable ovarian cancers. We will validate that there is no confounding with regards to demographics, risk factors and non-ovarian malignancies and non-neoplastic lesions. This project will provide the requisite data for future larger scale clinical validation. This novel paradigm could transform the clinical practice of ovarian cancer screening. We envision that this test can be performed by a gynecologist during an annual exam, similar to the pap-smear for cervical neoplasia. PUBLIC HEALTH RELEVANCE: Ovarian cancer is one of the deadliest of all major cancers with no effective screening currently available. We propose a new, minimally invasive ovarian cancer screening strategy that would be performed by a gynecologist during an annual exam, similar to the pap-smear for cervical neoplasia.